Because of the use of indoles in drug syntheses and in perfumery, the chemistry of the indoles has been investigated very thoroughly. However, the known preparations still do not offer a simple, easy synthesis to this group of chemicals. FOr example, the Fishcer Indole Synthesis, by which a phenylhydraxine of an aldehyde or ketone is heated in the presence of a catalyst such as zinc chloride, boron trifluoride or polyphosphoric acid, is complicated by the synthesis of the phenylhydrazine intermediate which involves tedious N-nitrosation and reduction steps. Furthermore, the reaction fails for indole itself. The Madelung Indole Synthesis, in which formotoluidine is reacted with potassium t-butoxide, is convenient because of the ready accessibility of the starting materials; but the reaction proceeds only at a high reaction temperature (300.degree. C.) and requires the decomposition of half of the intermediate pottassium O-formotoluidide to pottassium toluidide which in turn functions as a strong base to metalate the methyl proton of potassium formotoluidide and effect the cyclization to indole. Because of the aforementioned decomposition reaction mechanism, the reacion gives only a 30-40 percent yield and a lot of tar residue which makes the reaction mixture almost intractable.
Lorenz et al., J. Org. Chem., 30, 2531 (1965) disclose a promising modification of the Madelung synthesis in which N-(2-toly)-N'-methyl-N'-pheynlformamidines are cyclized with sodium N-methylanilide in refluxing N-methylaniline. But this process involves 4 to 5 steps, including a very slow high vacuum distillation of the N-(2-tolyl)-N'-methyl-N'phenylformamidine intermediate and the separation of the product from oil, which make the process industrially unattractive.
The Reissert Indole Syntheses uses O-nitrophenyl-pyruvic acids as reaction intermediates. Due to the electron withdrawing characteristic of the nitro group, O-nitrophenyl-ptruvis acids are obtainable by condensation of O- nitrotoluenes with diethyloxalate in the presence of a weak base, such as potassium tert-butoxide as catalyst. But the nitro group has to be reduced to amino group prior to the formation of the indole-2-carboxylic acids, which require further decarboxylation at 200.degree.-250.degree. C., to complete the preparation of indoles.